Metalated Nitriles: Unmasking Fundamental Reactivity

金属化腈：揭示基本反应性

• 批准号: 1464494
• 负责人: Fraser Fleming
• 金额: $ 41.75万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464494&HistoricalAwards=false
• 关键词: Metalated; Nitriles; Unmasking; Fundamental; Reactivity

Non-technical AbstractIn this project, funded by the Chemical Synthesis Program of the Chemistry Division, the research team is exploring fundamentally new reactions of nitriles. The proposal has impact in several areas; the elevation of nitrile chemistry, student training and development, and improving the ability of students' writing. The research falls into three broad areas that will develop new reactions of nitriles for the synthesis of cyclic, carbon-based scaffolds of relevance for the synthesis of pharmaceuticals, agrochemicals, and new materials. The first third of the proposal focuses on an extremely rapid synthesis of bicyclic nitriles, the middle third develops counter-intuitive methods of creating new carbon-carbon bonds, and the last section of the proposal develops new routes to reactive nitrile intermediates to control the three dimensional shape of nitrile-substituted scaffolds. The project continues an excellent track record in training students and post-doctoral associates, particularly minorities and women, to provide a stream of bright, highly motivated students for careers in science. The approach features vigorous research training with synergistic mentoring of undergraduate and graduate students and an emphasis on career life balance through group educational events and annual professional development retreats. Improved writing skills are taught through a review writing strategy that transitions undergraduate and graduate students from novice learners to expert practitioners. The approach simultaneously addresses a general writing deficiency in many students while instilling tools to critically evaluate the primary literature. Publishing the strategy in the Journal of Chemical Education should allow others to replicate the strategy with other students.Technical AbstractThis project focuses on a blend of conceptually new bond constructions and new chemical entities, many of which challenge conventional processes. Preliminary results demonstrate the feasibility of preparing chiral decalones in a single synthetic operation, potentially replacing multi-step technology based on the Wieland-Miescher ketone. A highly unusual equilibration is under development which changes the stereochemistry of a quaternary bridgehead center; a process that challenges conventional notions. A counter-intuitive alkylation of metalated nitriles with unactivated alkenes is rapidly assembling tricyclic ketones. A complementary alkene addition uses S-ketenimines as particularly attractive nucleophiles to address two long-standing challenges: rapid access to stable ketenimine nucleophiles, and nitrile-based alkenylations. The last section of the proposal provides an orthogonal, innovative asymmetric alkylation with metalated nitriles. Collectively, the proposed research exploits the unique reactivity of nitriles consummate with the long-term objective of elevating metalated nitrile alkylations to a level of influence comparable to that of enolate alkylations.

非技术摘要在这个由化学部化学合成计划资助的项目中，研究小组正在探索腈的新反应。该方案对提高腈类化学专业水平、学生的培养和发展、提高学生的写作能力等方面都有一定的影响。该研究福尔斯分为三个广泛的领域，将开发新的腈反应，用于合成与药物，农用化学品和新材料合成相关的环状碳基支架。该提案的前三分之一侧重于双环腈的快速合成，中间三分之一开发了创造新的碳-碳键的反直觉方法，提案的最后一部分开发了反应性腈中间体的新路线，以控制腈取代支架的三维形状。该项目继续在培训学生和博士后助理，特别是少数民族和妇女，提供了一个光明的，高度积极的学生在科学事业流的良好记录。该方法的特点是积极的研究培训与本科生和研究生的协同辅导，并通过集体教育活动和年度专业发展务虚会强调职业生活的平衡。提高写作技巧是通过一个审查写作策略，过渡本科生和研究生从新手学习者专家从业者教。这种方法同时解决了许多学生普遍的写作缺陷，同时灌输工具，批判性地评估主要文献。发表在化学教育杂志的战略应该允许其他人复制的战略与其他students.Technical AbstractThis项目的重点是概念上的新的键结构和新的化学实体的混合，其中许多挑战传统的过程。初步结果表明，在一个单一的合成操作中制备手性十氢萘酮的可行性，有可能取代基于Wieland-Miescher酮的多步技术。一个非常不寻常的平衡正在开发中，它改变了四元桥头中心的立体化学;一个挑战传统观念的过程。金属化腈与未活化烯烃的反直觉烷基化是快速组装三环酮。互补烯烃加成使用S-烯酮亚胺作为特别有吸引力的亲核试剂来解决两个长期存在的挑战：快速获得稳定的烯酮亚胺亲核试剂和基于腈的烯基化。该提案的最后一部分提供了一个正交的，创新的不对称烷基化与金属化腈。总的来说，拟议的研究利用腈的独特反应性，完善了将金属化腈烷基化提升到与烯醇化物烷基化相当的影响水平的长期目标。